Genistein Modulates Proliferation and Mitochondrial Functionality in Breast Cancer Cells Depending on ERalpha/ERbeta Ratio

Abstract

Breast cancer is the most common malignancy in women of developed countries. The aim of this study was to investigate whether genistein, a soy phytoestrogen, and 17β-estradiol (E2) could have effects on the cell cycle and mitochondrial function and dynamics. Three human breast cancer cell lines with different estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) ratio were used: MCF-7 (high ERα/ERβ ratio), T47D (low ERα/ERβ ratio) and MDA-MB-231 (ER-negative). Cell proliferation, cell cycle, mitochondrial functionality, and mitochondrial dynamics parameters were analyzed. E2 and genistein treatment induced cell proliferation and apoptosis inhibition in MCF-7, but not in T47D and MDA-MB-231. Moreover, genistein treatment produced an up-regulation of ERβ and a rise in cytochrome c oxidase activity in T47D cells, decreasing the ATP synthase/cytochrome c oxidase ratio. Finally, genistein treatment produced a drop in mitochondrial dynamics only in MCF-7 cells. In summary, the beneficial effects of genistein consumption depend on the ERα/ERβ ratio in breast cells. Therefore, genistein treatment produces cell cycle arrest and an improvement of mitochondrial functionality in T47D cells with a low ERα/ERβ ratio, but not in MCF-7 (high ERα/ERβ ratio) and MDA-MB-231 (ER-negative) ones.

The presence of Estrogen Receptor β modulates the response of breast cancer cells to therapeutic agents

“…Previous results obtained in our laboratory demonstrated the importance of the ER␣/ER␤ ratio in the maintenance of mitochondrial redox homeostasis (Nadal-Serrano et al, 2013;Pons et al, 2014;Sastre-Serra et al, 2013a;2012b). Thus, exposure to cells with a high ER␣/ER␤ ratio to 17␤-estradiol (E2) or genistein (GEN), a phytoestrogen capable to bind both ERs, provoked an increase in ROS production and a loss of mitochondrial functionality.…”

Genistein inhibits A549 human lung cancer cell proliferation via miR-27a and MET signaling

“…Genistein also has extensive pharmacological effects in animal cells. A previous study found that genistein has anticancer effects, including in vitro antitumor effects in human breast cancer cell lines (12) and prostate cancer cells (13). Thus, genistein is a potential cancer chemoprevention agent with a broad development prospect (14).…”

Calycosin and Genistein Induce Apoptosis by Inactivation of HOTAIR/p-Akt Signaling Pathway in Human Breast Cancer MCF-7 Cells

“…It has been shown that calycosin and genistein inhibit many types of cancers including breast cancer [4,5,6,7] through the regulation of several cell signaling pathways such as the mitogen-activated protein kinases (MAPK), Akt and JAK/STAT pathways [8,9,10]. …”